Effects of water deprivation on renal hydroelectrolytic excretion in chronically Trypanosoma cruzi-infected rats

The effect of an 8 hour-period of water deprivation on fluid and electrolyte renal excretion was investigated in male Wistar rats infected with the strain São Felipe (12SF) of Trypanosoma cruzi, in comparison with age and sex matched non-infected controls. The median percent reductions in the urinary flow (-40% v -63%) and excretion ofsodium (-57% v-79%) were smaller in chagasic than in control rats, respectively. So, chagasic rats excreted more than controls. On the other hand, the median percent decrement in the clearance of creatinine was higher in chagasic (-51%) than in controls (-39%). Thus, chagasic rats showed some disturbed renal hydroelectrolytic responses to water deprivation, expressed by smaller conservation, or higher excretion of water and sodium in association with smaller glomerularfiltration rate. This fact denoted an elevation in the fractional excretion of sodium and water.

Evaluation of platelet number and function and fibrinogen level in patients bitten by snakes of the Bothrops genus

Platelet function and plasma fibrinogen levels were evaluated in 14 patients, 10 males and 4females, aged 13-59years bitten by Bothrops genus snakes. There was a statistical difference (p < 0.05) among plasma fibrinogen levels evaluated 24 and 48 hours after envenomation. There was a tendency towards normalization after 48 hours of treatment. The low platelet number was clear in 24-48 hour evaluations with a tendency towards normalization after 48 hours of treatment (p<0.05). Fibrinogen levels and fibrin degradation product (FDP) levels appeared to be altered in 83.33% of patients evaluated. The authors suggest that platelet hypoaggregation is related to decreased fibrinogen and increased FDP levels.

The impact of Ireland’s current Mental Health Policy on the profile of community mental Health Services

RESUMO: Em 2006, foi aprovada uma nova política governamental para a saúde mental intitulada “Uma Visão para a Mudança”, a qual está neste momento no sétimo ano de implementação. A política descreve um enquadramento para o desenvolvimento e promoção da saúde mental positiva para toda a Comunidade e para a prestação de serviços acessíveis, baseados na comunidade, serviços especializados para pessoas com doença mental. A implementação da política e o tornar a “Vision for Change” uma realidade têm sido problemáticos, com críticas consideráveis por parte dos intervenientes, relativas à lenta e desconexa implementação. Este estudo fornece informação sobre as características dos serviços de três importantes tipos de instituições de saúde mental comunitária a nível nacional, nomeadamente Hospitais de Dia, Centros de Dia e residências comunitárias operantes 24 horas. A pesquisa analisa objetivos e funções, perfis dos pacientes, atividades terapêuticas, a eficácia das redes de comunicação e beneficia da perspectiva dos funcionários sobre o que mudou no terreno ao longo dos últimos sete anos. As questões identificadas a partir das características dos três serviços dizem respeito a todos. Os participantes indicaram que o ethos da recuperação parece ter alcançado um papel mais central no tratamento do paciente na comunidade mas reconheceram que o desafio de integrar os princípios de recuperação na prática clínica se mantém presente. Parece ser reconhecida a importância da planificação do cuidado individual nos serviços comunitários e os entrevistados indicaram que existe um empenho para garantir o envolvimento do usuário do serviço. Há diferenças entre os „pontos de vista do pessoal‟ e os „pontos de vista dos representantes‟ sobre uma série de aspetos da prestação de serviços. Este é o primeiro estudo irlandês deste género a examinar a prestação de serviços das três principais instituições comunitárias de saúde mental num só estudo. Estes serviços representam um enorme investimento em recursos, quer a nível monetário, quer humano. O estudo examinou os desafios e as questões fundamentais que lhe são aplicáveis e que têm impacto nestes três tipos de prestação de serviços. Também forneceu informações sobre os elementos de mudança positiva, os quais se começam a focar lentamente na prestação do serviço, assim como na importância da centralidade do utilizador do serviço e na promoção de um ethos da recuperação.----------ABSTRACT: In 2006, a new Government policy for mental health “A Vision for Change” was endorsed and is currently in the seventh year of implementation. The policy describes a comprehensive framework for building and fostering positive mental health across the entire community and for providing accessible, community based, specialist services for people with mental illness. The implementation of the policy and turning “Vision for Change” into reality has been problematic with considerable criticism from stakeholders concerning slow and disjointed implementation. This study provides information on three key community mental health service settings, namely Day Hospitals, Day Centres and 24 Hour Community Residences at a national level. The research looks at aims and functions, patient profiles, therapeutic activities, effectiveness of key communication networks and gains an insight from staff on what has changed on the ground over the past seven years. Issues identified from the three service settings pertain to all. Participants indicated that the recovery ethos appears to have moved to a more central role in patient care in the community but acknowledged that the challenge of integrating recovery principles in clinical practice remains present. The importance of individual care planning appears to be recognised in community services and respondents indicated that efforts are being made to ensure service user involvement. There were differences between „staff views‟ and „advocate views‟ on a number of aspects of service provision. This is the first Irish study of its kind to examine service provision across the three main community mental health settings in one study. These services represent a huge investment in resources both on a monetary and human level. This study has examined the challenges and key issues which are applicable and impacting on all three types of service provision. It has also provided information on the elements of positive change, which are slowly embedding themselves in service provision such as the importance of the centricity of the service user and the promotion of a recovery ethos.

Taxes and labor supply: Portugal, Europe, and the United States (Conference version)

I relate hours worked with taxes on consumption and labor. I propose a model and compare its predictions for Portugal, France, Spain, United Kingdom and United States. Hours per worker in Portugal decreased from 35.1 in 1986 to 32.6 in 2001. With only the parameters and the taxes for Portugal, the model predicts the hours worked in 2001 with an error of only 12 minutes from the actual hours. Across countries, most predictions differ from the data by one hour or less. The model is able to explain the trend in hours with only the changes in taxes.

Taxes and labor supply: Portugal, Europe, and the United States

I relate hours worked with taxes on consumption and labor for Portugal, France, Spain, United Kingdom and United States. From 1986 to 2001, hours per worker in Portugal decreased from 35.1 to 32.6. With the parameters for Portugal, the model predicts hours worked in 2001 with an error of only 12 minutes from the actual hours. Across countries, most predictions differ from the data by one hour or less. The model is not sensible to special assumptions on the parameters. I calculate the long run effects of taxes on consumption, hours, capital and welfare for Portugal. I extend the model to discuss implications for Social Security. I discuss the steady state and the transition from a pay-as-you-go to a fully funded system.

Target-specific multiphysics modeling for thermal medicine applications

Dissertation to obtain the degree of Doctor of Philosophy in Biomedical Engineering

Evaluation of the impact of chemical control measures and entomological surveillance on Chagas' disease in the counties of Mambaí and Buritinópolis, Goiás State, Brazil

Epidemiological surveillance activities were implemented in 1980 in Mambaí and Buritinópolis counties, Goiás State. Twenty years later the authors evaluated the impact of these vector control measures on Chagas' disease transmission, based on entomological indicators. Entomological investigation was conducted using the man-hour technique and covering all domiciles. In order to study vector food sources the stomach contents of triatomines were analyzed using the modified precipitins technique. Triatomines were shown to be present in 48 (71.6%) of the 67 locations. Peridomiciliary infestation rates in Mambaí and Buritinópolis were 8.7% and 12.1%, respectively, while intradomiciliary rates were 0.7% and 1.2%. Triatoma sordida was the species identified in 97.3% of all captured specimens. It was also the only species found to be naturally infected with Trypanosoma cruzi. Birds were the most frequent food source (45%) for Triatoma sordida. The most significant result was the complete absence of Triatoma infestans in the two counties.

Hábitos e problemas do sono das crianças dos 2 a 10 anos

RESUMO: Enquadramento: O sono é cada vez mais reconhecido como um fator determinante na Saúde Infantil porque, quando desadequado, pode ter consequências na regulação emocional e do comportamento, nas funções cognitivas, no rendimento académico, na regulação do peso e no risco de lesões acidentais. Os hábitos e problemas do sono das crianças portuguesas não se encontram ainda bem caracterizados. Este conhecimento é importante para o desenvolvimento da investigação e para a promoção da saúde nesta área. Objetivos: Adaptar e validar o Children's Sleep Habits Questionnaire (CSHQ) para a cultura portuguesa; Caracterizar os hábitos de sono de uma amostra de crianças dos 2 aos 10 anos tendo em vista a obtenção de dados de referência; Estimar a prevalência dos problemas do sono na perspetiva dos pais; Avaliar se existem diferenças nos hábitos e problemas do sono entre as regiões de média-alta e baixa densidade populacional; Identificar potenciais consequências dos problemas do sono. Métodos: Foi realizado um estudo transversal, descritivo e correlacional. A versão portuguesa do questionário (CSHQ-PT) foi desenvolvida de acordo com as orientações previamente publicadas e validada numa amostra de 315 crianças dos 2 aos 10 anos. Para o estudo dos hábitos e problemas do sono, o CSHQ-PT foi distribuído aos pais de 2257 crianças recrutadas em 17 zonas de agrupamentos escolares (15 escolhidos de forma aleatória) das áreas da Grande Lisboa, Península de Setúbal e Alentejo, compreendendo zonas litorais e do interior, e de alta, média e baixa densidade populacional. Foram obtidos 1450 (64%) questionários válidos. Resultados: O CSHQ-PT mostrou propriedades psicométricas semelhantes às das versões de outros países e adequadas para a investigação. A avaliação dos hábitos de sono nos dias de semana mostrou que as crianças se deitam, em média, pelas 21h 44m (DP 38 min.). A necessidade da companhia dos pais para adormecer diminui com a idade, ocorrendo em 49% das crianças aos 2-3 anos e 10% aos 9-10 anos. O hábito de adormecer a ver televisão foi descrito em 15,8% das crianças. O tempo total de sono diário diminui com a idade, com uma diferença mais marcada dos 2 para os 3 anos e dos 3 para os 4 anos, quando a sesta se torna menos frequente. No fim de semana, 25% das crianças dormia pelo menos mais uma hora. As diferenças nos hábitos de sono entre regiões de média-alta e de baixa densidade populacional foram reduzidas, sem reflexo na duração média do sono. Considerando valores de referência de outros países, verificou-se que 10% das crianças estudadas tinha uma duração do sono dois desvios-padrão abaixo da média esperada para a idade. A prevalência dos problemas do sono na perspetiva dos pais foi de 10,4%, sem diferenças significativas entre classes etárias, subgrupos de nível educacional dos pais, nem entre zonas de média-alta e baixa densidade populacional. Estes problemas do sono mostraram-se associados, sobretudo, à duração do sono insuficiente, resistência em ir para a cama, dificuldade em adormecer sozinho, despertares noturnos frequentes e ocorrência de parassónias. A baixa prevalência de problemas do sono identificados pelos pais contrasta com cotações elevadas no CSHQ-PT que traduzem comportamentos-problema mais frequentes, que são bem aceites por alguns pais. O Índice de Perturbação do Sono foi mais elevado nas famílias com menor nível educacional. Em análise multivariada mostraram valor preditivo para a sonolência diurna: o tempo total de sono diário, a diferença da duração do sono noturno durante a semana e no fim de semana, a frequência de algumas parassónias e o hábito de adormecer a ver televisão. O rendimento escolar mostrou associação com os problemas do sono, que são mais frequentes nas crianças com dificuldades escolares e hiperatividade/problemas de atenção. A relação entre estas variáveis é complexa. Conclusões: Este estudo mostrou que os problemas comportamentais do sono e a privação de sono são frequentes na população estudada. Estes problemas têm consequências, uma vez que correspondem a uma frequência mais elevada de sintomas de sonolência diurna, por comparação com outros países. Perante este cenário, é muito importante reforçar a promoção de hábitos de sono saudáveis e continuar a estudar as consequências do sono desadequado nas crianças portuguesas. -----------ABSTRACT:Framework: Sleep is increasingly being recognized as important to Child Health, for inadequate sleep may impact behavioral and emotional regulation, cognitive functions, academic performance, weight regulation and the risk of accidental injuries. The sleep habits and sleep problems of Portuguese children are not well characterized. This knowledge is important to support further studies and health promotion actions. Objectives: Develop and validate a Portuguese version of the Children's Sleep Habits Questionnaire (CSHQ-PT); Characterize the sleep habits and problems in a sample of Portuguese children from the ages of 2 to 10 for future reference; Estimate the prevalence of parent-defined sleep problems; Assess whether there are differences in sleep habits and problems between regions of medium-high and low population densities; Identify potential consequences of sleep problems. Methods: We conducted a cross-sectional, descriptive and correlational study. The Portuguese version of the questionnaire (CSHQ-PT) was developed according to published guidelines and validated in a sample of 315 children from 2 to 10 years old (y.o.). In order to study sleep habits and problems we delivered the CSHQ-PT to 2257 children recruited from 17 school districts (15 were chosen randomly) in areas with low, medium and high population densities, including coastline and inland regions. 1450 (64%) valid questionnaires were obtained. Results: The CSHQ-PT demonstrated psychometric properties that were similar to the versions from other countries and adequate for research. The evaluation of sleep habits showed that on schooldays children go to bed, on average, at 21h 44m (SD 38 min.). The need of having the parent in the room at bedtime decreases with the age of the child, occurring in 49% of children with 2-3 y.o. and 10% of children between 9 and 10 y.o. The habit of going asleep while watching TV was reported in 15,8% of the children. Total sleep time diminishes with the age of the child, having a major decrease from 2 to 3 y.o. and from 3 to 4 y.o., along with less frequent naps. During the weekend, 25% of the children sleep at least one extra hour. Considering reference values from other series, we found that 10% of the children had a sleep duration two standard deviations below the mean for the age. The differences in sleep habits between regions of medium-high and low population densities are few, and there are no differences in average sleep durations. The prevalence of parent-defined sleep problems was 10.4%. There were no significant differences between age classes, parent education subgroups or between regions of medium-high and low population densities. These sleep problems were associated with insufficient sleep duration, bedtime resistance, difficulty in falling asleep alone, frequent night awakenings and the occurrence of parasomnias. The low prevalence of parent-defined sleep problems contrasts with high CSHQ scores meaning that problematic behaviors are more frequent, but acceptable to some parents. The Sleep Disturbance Score was higher in families with a lower educational level. In multivariate analysis, the following factors predicted the daytime somnolence score: total sleep time, the difference in night sleep duration between the weekend and school days, the frequency of some parasomnias and the habit of falling asleep while watching TV. School achievement showed a negative correlation with the sleep problems, which are more frequent in children with school difficulties and hyperactivity/attention problems. The relationship between these variables is complex. Conclusions: This study evidenced that behavioral sleep problems and sleep deprivation are common in our population. These sleep problems have consequences as they correspond to more symptoms of excessive daytime somnolence comparing to other countries. Therefore, we reinforce the importance of promoting healthy sleep habits and further study the consequences of inadequate sleep in Portuguese children.

Functional genomic analysis of heat stress in Vitis vinifera

Grapevine (Vitis vinifera) is one of most agro-economically important fruit crops worldwide, with a special relevance in Portugal where over 300 varieties are used for wine production. Due to global warming, temperature stress is currently a serious issue affecting crop production especially in temperate climates. Mobile genetic elements such as retrotransposons have been shown to be involved in environmental stress induced genetic and epigenetic modifications. In this study, sequences related to Grapevine Retrotransposon 1 (Gret1) were utilized to determine heat induced genomic and transcriptomic modifications in Touriga Nacional, a traditional Portuguese grapevine variety. For this purpose, growing canes were treated to 42 oC for four hours and leaf genomic DNA and RNA was utilized for various techniques to observe possible genomic alterations and variation in transcription levels of coding and non-coding sequences between non-treated plants and treated plants immediately after heat stress (HS-0 h) or after a 24 hour recovery period (HS-24 h). Heat stress was found to induce a significant decrease in Gret1 related sequences in HS-24 h leaves, indicating an effect of heat stress on genomic structure. In order to identify putative heat induced DNA modifications, genome wide approaches such as Amplified Fragment Length Polymorphism were utilized. This resulted in the identification of a polymorphic DNA fragment in HS-0 h and HS-24 h leaves whose sequence mapped to a genomic region flanking a house keeping gene (NADH) that is represented in multiple copies in the Vitis vinifera genome. Heat stress was also found to affect the transcript levels of various non-coding and gene coding sequences. Accordingly, quantitative real time PCR results established that Gret1 related sequences are up regulated immediately after heat stress whereas the level of transcript of genes involved in identification and repair of double strand breaks are significantly down regulated in HS-0 h plants. Taken together, the results of this work demonstrated heat stress affects both genomic integrity and transcription levels.

Photochemical degradation of triclosan: a comparison between different light sources

New emerging contaminants could represent a danger to the environment and Humanity with repercussions not yet known. One of the major worldwide pharmaceutical and personal care productions are antimicrobials products, triclosan, is an antimicrobial agent present in most products. Despite the high removal rate of triclosan present in wastewater treatments, triclosan levels are on the rise in the environment through disposal of wastewater effluent and use of sewage sludge in land application. Regulated in the EC/1272/2008 (annex VI, table 3.1), this compound is considered very toxic to aquatic life and it has been reported that photochemical transformation of triclosan produces dioxins. In the current work it was defined three objectives; determination of the most efficient process in triclosan degradation, recurring to photochemical degradation methods comparing different sources of light; identification of the main by-products formed during the degradation and the study of the influence of the Fenton and photo-Fenton reaction. Photochemical degradation methods such as: photocatalysis under florescent light (UV), photocatalysis under visible light (sunlight), photocatalysis under LEDs, photo-Fenton and Fenton reaction have been compared in this work. The degradation of triclosan was visualized through gas chromatography/mass spectrometry (GC/MS). In this study photo-Fenton reaction has successfully oxidized triclosan to H2O and CO2 without any by-products within 2 hours. Photocatalysis by titanium dioxide (TiO2) under LEDs was possible, having a degradation rate of 53% in an 8 hours essay. The degradation rate of the Fenton reaction, UV light and sunlight showed degradation between 90% and 95%. The results are reported to the data observed without statistic support, since this was not possible during the work period. Hydroquinone specie and 2,4-dichlorophenol by-products were identified in the first hour of photocatalysis by UV. A common compound, possibly identified has C7O4H , was present at the degradation by UV, sunlight and LEDs and was concluded to be a contaminant. In the future more studies in the use of LEDs should be undertaken given the advantages of long durability and low consumption of energy of these lamps and that due to their negative impact on the environment fluorescent lamps are being progressively made unavailable by governments, requiring new solutions to be found. Fenton and photo-Fenton reactions can also be costly processes given the expensive reagents used.

Ecology of phlebotomines (Diptera, Psychodidae) in rural foci of leishmaniasis in tropical Brazil

INTRODUCTION: This work aimed to study the community structure of sandflies, with regard to the richness, constancy, abundance, and monthly frequency of the species with a focus on the transmission of leishmaniasis. METHODS: The study was conducted in the rural villages of Bom Jardim and Santa Maria, situated on the edge of a tropical rain forest in the municipality of São Jose de Ribamar, Maranhão, Brazil. The phlebotomines were captured in the intradomiciles and peridomiciles of each village, with Centers for Disease Control (CDC) light traps set in 10 homes in each village, for 1 year, once a month, from 18h to 6h. RESULTS: We collected 1,378 individuals of 16 sandfly species. The capture success rate was higher in Bom Jardim (0.61 specimens/hour/trap) than that of Santa Maria (0.35/specimens/hour/trap). The sandflies were more abundant in the peridomiciles (86.1%) and in the rainy season (77%). Five species were considered constants (occurring in more than 50% of samples), 5 accessory (25%-50%), and 6 accidental (<25%). The most abundant species were Lutzomyia longipalpis (59.7%) and L whitmani (28%). The permutation analysis showed differences between the species composition of the villages and no separation between the intradomicile and peridomicile of each village. The species that most contributed to the dissimilarity between the light traps of the 2 villages were L. longipalpis, L. whitmani, and L. evandroi, contributing to 80.8% of the variation among groups. CONCLUSIONS: The high level of richness and abundance of species and the presence of competent vectors throughout the year and around houses justify the occurrence of leishmaniasis cases reported in the area.

Triatomines in dwellings and outbuildings in an endemic area of Chagas disease in northeastern Brazil

INTRODUCTION: The present study identified the triatomines collected in intra and peri-domestic environments, observed the occurrence of Trypanosoma cruzi infection in triatomines and correlated this information with housing conditions and the fauna associated with the rural areas of the City of Itabaianinha, located in the State of Sergipe, Brazil. METHODS: Quarterly visits were conducted between March 2009 and March 2010, and the homes to be visited for the active search of insects were determined by random selection. In each housing unit, the insects were collected by a manual search with a metal clip and flashlight to inspect openings and cavities, with a collection time of one hour/home/individual. The Pirisa® dislodge chemical was used to force the insects to leave their ecotopes. Analysis of the intestinal contents of triatomines was performed in the laboratory to establish the presence of Trypanosomatidae. RESULTS: Of the 103 dwellings surveyed, 17.5% were infested with Panstrongylus megistus. The village of Mutuca exhibited the highest infestation rate (38.1%). All the villages with relevant infestation rates were situated in the northern area of the city. The highest percentage of vector infection was found in the village of Água Boa (56.5%). The rural dwellings were found to be primarily brick or wooden house with or without roughcast or plastered walls, and the outbuilding most frequently associated with triatomines was the chicken run. CONCLUSIONS: These results emphasise the need for broader vector control and surveillance and for educational campaigns in the context of the Chagas Disease Control Program.

Evaluation of antihypertensive drugs in patients with obstructive sleep apnea and in rats submitted to chronic intermittent hypoxia

RESUMO: A hipertensão arterial (HA) é uma patologia altamente prevalente, embora claramente subdiagnosticada, em doentes com síndrome de apneia obstrutiva do sono (SAOS). Estas duas patologias apresentam uma estreita relação e a monitorização ambulatória da pressão arterial (MAPA), por um período de 24 horas, parece ser o método mais preciso para o diagnóstico de hipertensão em doentes com SAOS. No entanto, esta ferramenta de diagnóstico para além de ser dispendiosa e envolver um número acrescido de meios técnicos e humanos, é mais morosa e, por conseguinte, não é utilizada por rotina no contexto do diagnóstico da SAOS. Por outro lado, apesar da aplicação de pressão positiva contínua nas vias aéreas (CPAP – Continous Positive Airway Pressure) ser considerada a terapêutica de eleição para os doentes com SAOS, o seu efeito no abaixamento da pressão arterial (PA) parece ser modesto, exigindo, por conseguinte, a implementação concomitante de terapêutica anti-hipertensora. Acontece que são escassos os dados relativos aos regimes de fármacos anti-hipertensores utilizados em doentes com SAOS e, acresce ainda que, as guidelines terapêuticas para o tratamento farmacológico da HA, neste grupo particular de doentes, permanecem, até ao momento, inexistentes. A utilização de modelos animais de hipóxia crónica intermitente (CIH), que mimetizam a HA observada em doentes com SAOS, revela-se extremamente importante, uma vez que se torna imperativo identificar fármacos que promovam um controle adequado da PA neste grupo de doentes. No entanto, estudos concebidos com o intuito de investigar o efeito anti-hipertensor dos fármacos neste modelo animal revelam-se insuficientes e, por outro lado, os escassos estudos que testaram fármacos anti-hipertensores neste modelo não foram desenhados para responder a questões de natureza farmacológica. Acresce ainda que se torna imprescindível garantir a escolha de um método para administração destes fármacos que seja não invasivo e que minimize o stress do animal. Embora a gavagem seja uma técnica indiscutivelmente eficaz e amplamente utilizada para a administração diária de fármacos a animais de laboratório, ela compreende uma sequência de procedimentos geradores de stress para os animais e, que podem por conseguinte, constituir um viés na interpretação dos resultados obtidos. O objectivo global da presente investigação translacional foi contribuir para a identificação de fármacos anti-hipertensores mais efectivos para o tratamento da HT nos indivíduos com SAOS e investigar mecanismos subjacentes aos efeitos sistémicos associadas à SAOS bem como a sua modulação por fármacos anti-hipertensores. Os objectivos específicos foram: em primeiro lugar,encontrar novos critérios, baseados nas medidas antropométricas, que permitam a identificação de doentes com suspeita de SAOS, que erroneamente se auto-classifiquem como nãohipertensos, e desta forma promover um uso mais criterioso do MAPA; em segundo lugar, investigar a existência de uma hipotética associação entre os esquemas de fármacos antihipertensores e o controle da PA (antes e após a adaptação de CPAP) em doentes com SAOS em terceiro lugar, avaliar a eficácia do carvedilol (CVD), um fármaco bloqueador β-adrenérgico não selectivo com actividade antagonista α1 intrínseca e propriedades anti-oxidantes num modelo animal de hipertensão induzida pela CIH; em quarto lugar, explorar os efeitos da CIH sobre o perfil farmacocinético do CVD; e, em quinto lugar, investigar um método alternativo à gavagem para a administração crónica de fármacos anti-hipertensores a animais de laboratório. Com este intuito, na primeira fase deste projecto, fizemos uso de uma amostra com um número apreciável de doentes com SAOS (n=369), que acorreram, pela primeira vez, à consulta de Patologia do Sono do CHLN e que foram submetidos a um estudo polissonográfico do sono, à MAPA e que preencheram um questionário que contemplava a obtenção de informação relativa ao perfil da medicação anti-hipertensora em curso. Numa segunda fase, utilizámos um modelo experimental de HT no rato induzida por um paradigma de CIH. Do nosso trabalho resultaram os seguintes resultados principais: em primeiro lugar, o índice de massa corporal (IMC) e o perímetro do pescoço (PP) foram identificados como preditores independentes de “auto-classificação errónea” da HA em doentes com suspeita de SAOS; em segundo lugar, não encontramos qualquer associação com significado estatístico entre os vários esquemas de fármacos anti-hipertensores bem como o número de fármacos incluídos nesse esquemas, e o controle da PA (antes e depois da adaptação do CPAP); em terceiro lugar, apesar das doses de 10, 30 e 50 mg/kg de carvedilol terem promovido uma redução significativa da frequência cardíaca, não foi observado qualquer decréscimo na PA no nosso modelo animal; em quarto lugar, as razões S/(R+S) dos enantiómeros do CVD nos animais expostos à CIH e a condições de normóxia revelaram-se diferentes; e, em quinto lugar, a administração oral voluntária mostrou ser um método eficaz para a administração diária controlada de fármacos anti-hipertensores e que é independente da manipulação e contenção do animal. Em conclusão, os resultados obtidos através do estudo clínico revelaram que o controle da PA, antes e após a adaptação do CPAP, em doentes com SAOS é independente, quer do esquema de fármacos anti-hipertensores, quer do número de fármacos incluídos num determinado esquema. Os nossos resultados salientam ainda a falta de validade da chamada self-reported hypertension e sugerem que em todos os doentes com suspeita de SAOS, com HA não diagnosticada e com um IMC e um PP acima de 27 kg/m2 e 39 cm, respectivamente, a confirmação do diagnóstico de HA deverá ser realizada através da MAPA, ao invés de outros métodos que com maior frequência são utilizados com este propósito. Os resultados obtidos no modelo animal de HA induzida pela CIH sugerem que o bloqueio do sistema nervoso simpático, juntamente com os supostos efeitos pleiotrópicos do CVD, não parece ser a estratégia mais adequada para reverter este tipo particular de hipertensão e indicam que as alterações farmacocinéticas induzidas pela CIH no ratio S/(R+S) não justificam a falta de eficácia anti-hipertensora do CVD observada neste modelo animal. Por último, os resultados do presente trabalho suportam ainda a viabilidade da utilização da administração oral voluntária, em alternativa à gavagem, para a administração crónica de uma dose fixa de fármacos anti-hipertensores.---------------------------- ABSTRACT: Hypertension (HT) is a highly prevalent condition, although under diagnosed, in patients with obstructive sleep apnea (OSA). These conditions are closely related and 24-hour ambulatory blood pressure monitoring (ABPM) seems to be the most accurate measurement for diagnosing hypertension in OSA. However, this diagnostic tool is expensive and time-consuming and, therefore, not routinely used. On the other hand, although continuous positive airway pressure (CPAP) is considered the gold standard treatment for symptomatic OSA, its lowering effect on blood pressure (BP) seems to be modest and, therefore, concomitant antihypertensive therapy is still required. Data on antihypertensive drug regimens in patients with OSA are scarce and specific therapeutic guidelines for the pharmacological treatment of hypertension in these patients remain absent. The use of animal models of CIH, which mimic the HT observed in patients with OSA, is extremely important since it is imperative to identify preferred compounds for an adequate BP control in this group of patients. However, studies aimed at investigating the antihypertensive effect of antihypertensive drugs in this animal model are insufficient, and most reports on CIH animal models in which drugs have been tested were not designed to respond to pharmacological issues. Moreover, when testing antihypertensive drugs (AHDs) it becomes crucial to ensure the selection of a non-invasive and stress-free method for drug delivery. Although gavage is effective and a widely performed technique for daily dosing in laboratory rodents, it comprises a sequence of potentially stressful procedures for laboratory animals that may constitute bias for the experimental results. The overall goal of the present translational research was to contribute to identify more effective AHDs for the treatment of hypertension in patients with OSA and investigate underlying mechanisms of systemic effects associated with OSA, as well as its modulation by AHDs. The specific aims were: first, to find new predictors based on anthropometric measures to identify patients that misclassify themselves as non-hypertensive, and thereby promote the selective use of ABPM; second, to investigate a hypothetical association between ongoing antihypertensive regimens and BP control rates in patients with OSA, before and after CPAP adaptation; third, to determine, in a rat model of CIH-induced hypertension, the efficacy of carvedilol (CVD), a nonselective beta-blocker with intrinsic anti-α1-adrenergic activity and antioxidant properties; fourth, to explore the effects of CIH on the pharmacokinetics profile of CVD and fifth, to investigate an alternative method to gavage, for chronic administration of AHDs to laboratory rats. For that, in the first phase of this project, we used a sizeable sample of patients with OSA (n=369), that attended a first visit at Centro Hospitalar Lisboa Norte, EPE Sleep Unit, and underwent overnight polysomnography, 24-h ABPM and filled a questionnaire that included ongoing antihypertensive medication profile registration. In the second phase, a rat experimental model of HT induced by a paradigm of CIH that simulates OSA was used. The main findings of this work were: first, body mass index (BMI) and neck circumference (NC) were identified as independent predictors of hypertension misclassification in patients suspected of OSA; second, in patients with OSA, BP control is independent of both the antihypertensive regimen and the number of antihypertensive drugs, either before or after CPAP adaptation; third, although the doses of 10, 30 and 50 mg/Kg of CVD promoted a significant reduction in heart rate, no decrease in mean arterial pressure was observed; fourth, the S/(R+S) ratios of CVD enantiomers, between rats exposed to CIH and normoxic conditions, were different and fifth, voluntary ingestion proved to be an effective method for a controlled daily dose administration, with a define timetable, that is independent of handling and restraint procedures. In conclusion, the clinical study showed that BP control in OSA patients is independent of both the antihypertensive regimen and the number of antihypertensive drugs. Additionally, our results highlight the lack of validity of self-reported hypertension and suggest that all patients suspected of OSA with undiagnosed hypertension and with a BMI and NC above 27 Kg/m2 and 39 cm should be screened for hypertension, through ABPM. The results attained in the rat model of HT related to CIH suggest that the blockade of the sympathetic nervous system together with the putative pleiotropic effects of carvedilol is not able to revert hypertension induced by CIH and point out that the pharmacokinetic changes induced by CIH on S/(R+S) ratio are not apparently responsible for the lack of efficacy of carvedilol in reversing this particular type of hypertension. Finally, the results here presented support the use of voluntary oral administration as a viable alternative to gavage for chronic administration of a fixed dose of AHDs.

Composition, abundance and aspects of temporal variation in the distribution of Anopheles species in an area of Eastern Amazonia

Introduction The diverse and complex environmental conditions of the Amazon Basin favor the breeding and development of Anopheles species. This study aimed to describe the composition, abundance and temporal frequency of Anopheles species and to correlate these factors with precipitation, temperature and relative humidity. Methods The study was conducted in the District of Coração, State of Amapá, Brazil. Samples were collected monthly during three consecutive nights, from 6:00 PM to 10:00 PM, from December 2010 to November 2011. In addition, four 12-hour collections (i.e., 6:00 PM to 6:00 AM) were performed during this period. Results A total of 1,230 Anopheles specimens were collected. In the monthly collections, Anopheles darlingi was the predominant species, followed by An. braziliensis and An. albitarsis s.l., whereas An. darlingi, An. peryassui and An. braziliensis were the most frequent species collected in the 12-hour collections. The greatest number of anophelines was collected in September (the dry season). The highest frequency of anophelines was observed for An. darlingi during September, when there were the least rainfalls of the year, along with lower relative humidity and higher temperatures. There was little variation in the abundance of this species in other months, with the exception of slight increases in February, July and August. Conclusions The major malaria vectors, An. darlingi and An. albitarsis s.l. (likely An. marajoara), were the most abundant species collected in the study area. Consequently, prevention and control measures should be taken to prevent malaria outbreaks in the District of Coração.

Reflux esophagitis and gastroesophageal reflux disease: a cross-sectional study of gastroesophageal reflux disease patients by age group

The purpose of this study was to explore the relationship between the intensity of acid reflux and severity of esophageal tissue damage in a cross-sectional study of patients with gastroesophageal reflux disease (GERD). Seventy-eight patients with were selected in accordance with the strict 24-hour ambulatory esophageal pHmetry (24h-pHM) criteria and distributed into three age groups: Group A: 14 - 24 years of age. Group B: 25 - 54; and Group C: 55 - 64. The 24h-pHM was carried out in accordance with DeMeester standardization, and the Savary-Miller classification for the diagnosis of reflux esophagitis was used. The groups were similar in 24h-pHM parameters (p > 0.05), having above normal values. For the study group as a whole, there was no correlation between age group and intensity of acid reflux, and there was no correlation between intensity of acid reflux and severity of esophageal tissue damage. However, when the same patients were sub-grouped in accordance with the depth of their epithelial injury and then distributed into age groups, there was a significant difference in esophagitis without epithelial discontinuity. Younger patients had less epithelial damage than older patients. Additionally, although there was a significant progression from the least severe to the moderate stages of epithelial damage among the age groups, there was no apparent difference among the age groups in the distribution between the moderate stages and most severe stages. The findings support the conclusion that the protective response of individuals to acid reflux varies widely. Continued aggression by acid reflux appears to lead to the exhaustion of individual mechanisms of epithelial protection in some patients, but not others, regardless of age or duration of the disease. Therefore, the diagnosis and follow-up of GERD should include both measurements of the quantity of refluxed acid and an assessment of the damage to the esophageal epithelium.